The Animal Core Unit will be responsible for the procurement, maintenance, surgical manipulation, and treatment of viral antibody free (vAF) experimental animals in the Program Project. These are services not provided by Department of Animal Medicine through its per diem charge which includes only food, water, bedding, and cage cleaning. All Program Project experiments will utilize VAF animals housed in a limited access facility designed to maintain the highest degree of cleanliness. The emphasis on VAF animals will preclude contamination of outcomes by infectious agents. Viral infection in particular not only affects the survival of transplant recipients but also modulates many of the processes to be studied in this Program. The objectives and responsibilities of the Program Project Animal Core Unit are as follows: 1. Provision of viral antibody free (vAF) animals and the maintenance of quarantine Procurement, quarantine, and housing arrangements and overall responsibility for the maintenance and verification of viral antibody free status of animals used in this Project 2. Selective breeding of transgenic and knockout founders and progeny, and congenic strains as directed by program directors Transgenic mice expressing a TcR specific for H-2 Ld class I MHC expressed on CD8+ T cells, CD40 transgenic and knockout mice, CD40L knockout mice, B7 transgenic and knockout mice, and other mutants as described in the individual Projects 3. Experimental manipulation of animals while maintaining VAF status as required by Program Project investigators Administration of reagents, including anti-CD4OL, other monoclonal antibodies, and other specific agents to be developed in the course of the Program; administration of cells in both adoptive transfer and immune system reconstitution studies; preparation of biopsy specimens (e.g. lymph nodes, peripheral blood) obtained under conditions that permit continued VAF status; maintenance of scid mice bearing hybridomas 4. Surgery: Creation and maintenance of dorsal skinfold chambers for intravital microscopic study of allogeneic and xenogeneic islet grafts and the performance of skin grafts 5. Testing for diabetes and skin graft rejection In brief, the Animal Core will provide essential assistance to each Program Project with the management and execution of in vivo studies conducted under viral antibody free conditions. It will maintain all records of animals and procedures and serve as a central facility for the cooperative efforts of the program projects.